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Zika virus and microcephaly: Antivaccine warriors say it’s vaccines that did it!

Last week, I wrote about how conspiracy theories have been flowing fast and furious about the Zika virus and microcephaly. Even if you didn’t see that post (perhaps instead having seen this one), you’ve probably seen the news reports describing how last fall the observation of a large number of cases of microcephaly, characterized by an abnormally small head and delayed brain development, in Brazil led researchers investigating the problem to suspect a link to a virus. That virus, the Zika virus, as you recall, is a mosquito-borne flavivirus related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes (photo source here). On the surface, this virus would appear to be a relatively benign virus, with 80% of its infections being asymptomatic and infections in the other 20% manifesting themselves as a self-limited, relatively mild flu-like viral illness characterized by fever, rash, arthralgia (joint aches), and conjunctivitis. Then came the evidence that prenatal infection might cause microcephaly.

As I discussed in my first post, the epidemiological link between Zika virus and microcephaly is not a slam dunk by any stretch of the imagination. It’s not even clear that there has been a major spike in incidence of microcephaly in Brazil. However, the evidence thus far is definitely sufficient to be suggestive of a link, such that further investigation is certainly warranted and perhaps precautions for women in the affected areas would be wise. None of this uncertainty has stopped the conspiracy theorists, of course. As we will see, the bizarre conspiracies are still coming. Perhaps the oddest of them are the ones from antivaccinationists, including a crank group of physicians that I haven’t discussed in a while. I’ll get to them in a moment.

First, however, I can’t help but mention that the CDC has published a new report on Zika virus for its latest issue of the Morbidity and Mortality Weekly Report (MMWR), Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses — Brazil, 2015. This report describes the result of Zika virus assays developed by the CDC for testing formalin-fixed, paraffin-embedded (FFPE) tissue samples. (This is what pathologists routinely do to fix any tissue removed during biopsies or surgery.) In December, the CDC tested tissues from two newborns with microcephaly who died within 20 hours of birth and two miscarriages (fetal loss at 11 and 13 weeks). They all came from the state of Rio Grande do Norte in Brazil, and all four mothers had had clinical signs of Zika virus infection, complete with fever and rash, during the first trimester of pregnancy but had no signs of active infection at the time of delivery or miscarriage. Tissues subjected to testing included brain and other autopsy tissues from the two newborns, a placenta from one of the newborns, and products of conception from the two miscarriages.

These tissues were subjected to reverse transcription-polymerase chain reaction (RT-PCR) directed at the gene for the nonstructural protein 5 and envelope genes using commonly used methods for RT-PCR. Tissues were also subjected to immunohistochemistry (using antibodies to identify specific proteins in tissues) using an anti-Zika virus antibody. This is what the CDC found:

For both newborns, significant histopathologic changes were limited to the brain, and included parenchymal calcification, microglial nodules, gliosis, and cell degeneration and necrosis. Other autopsy tissues and placenta had no significant findings. Tests for toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV were negative in the two mothers who experienced miscarriages. Placental tissue from one miscarriage showed heterogeneous chorionic villi with calcification, fibrosis, perivillous fibrin deposition, and patchy intervillositis and focal villitis, while tissue from the other miscarriage had sparsely sampled normal-appearing chorionic villi.

This report describes evidence of a link between Zika virus infection and microcephaly and fetal demise through detection of viral RNA and antigens in brain tissues from infants with microcephaly and placental tissues from early miscarriages. Histopathologic findings indicate the presence of Zika virus in fetal tissues. These findings also suggest brain and early gestational placental tissue might be the preferred tissues for postmortem viral diagnosis. Nonfrozen, formalin-fixed specimens or FFPE blocks are the preferred sample type for histopathologic evaluation and immunohistochemistry, and RT-PCR can be performed on either fresh frozen or formalin-fixed specimens. To better understand the pathogenesis of Zika virus infection and associated congenital anomalies and fetal death, it is necessary to evaluate autopsy and placental tissues from additional cases, and to determine the effect of gestational age during maternal illness on fetal outcomes.

In other words, the brains showed evidence of cellular degeneration and necrosis (cell death), and the placenta from one of the miscarriages had evidence of inflammation. The importance of these findings is that it shows that the Zika virus can infect the fetus when the mother is infected and that it appears to favor infecting the brain. Obviously, only four individuals are not enough to draw any sort of generalizable conclusions about prenatal Zika virus infection, but these results do provide evidence for biological plausibility of the hypothesis that prenatal Zika virus infection might be causing an outbreak of microcephaly. Still, there are many questions, such as why there haven’t been outbreaks like this before, given that Zika virus has been endemic in many areas since at least the 1950s and there have been outbreaks of Zika virus before in Africa, southeast Asia, and the Pacific Islands, as well as several countries in Central and South America where Zika virus outbreaks are currently being reported. Yet, despite how widespread the virus is, there haven’t been reports of increased incidence of microcephaly before this.

As I said the first time I discussed this issue, the whole question of whether Zika virus is causing microcephaly is complicated. Of course, if there’s one thing that attracts answers that are simple and wrong, it’s complex epidemiological questions about whether a given putative etiological agent is actually causing the disease or condition that it’s suspected of causing. No wonder antivaccine loons are all over the case! Sure, there’s the usual nonsense about how Zika virus is nothing more than a fake disease invented by an unholy cabal of the CDC, big pharma, and the World Health Organization (WHO), apparently all in order to contribute to Bill Gates’ global depopulation campaign, but one of the dumber antivaccine conspiracy theorists, the pseudonymous Levi Quackenboss, couldn’t resist asking:

Being the quack that I am, three questions first came to mind.

  1. What is the pesticide regulation situation in Brazil?
  2. Is there a Zika virus vaccine coming down the turnpike?
  3. Have prenatal vaccines been recently introduced to Brazilian women

Of course, Quackenboss forgot the most awesome conspiracy theory about Zika virus I’ve heard thus far, that the cause is genetically modified mosquitos that I discussed in my last post. Not surprisingly, Quackenboss’ answers to all three questions are yes, yes, and yes. She goes on about how Brazil uses a lot of pesticides, which if true is not good of course. She discusses voltage-gated sodium channels in a manner that amused me, because it’s so clear that he’s just showing off to his fellow antivaxers that she knows science, ma-an—or at least thinks she does. Truly, the arrogance of ignorance engendered by the Dunning-Kruger effect is strong in this one. (Ironically, I gave a talk to an ion channel conference held in London in September and have a grant to look at voltage-gated sodium channel function—among other things—as a potential target for breast cancer therapy; so I’m geeking out here. I also know a lot about certain sodium channels.) It turns out that specific pesticides disrupt voltage-gated sodium channel function, something that is well known. It also turns out that Quackenboss found an eleven year old review article that points this out and also notes that anticonvulsants (many of which interfere with voltage-gated sodium channel function) have been associated with birth defects, including microcephaly. Not surprisingly, Quackenboss neglects to mention the other part of the article that give the caveat, “there are currently no data to suggest that developmental exposure to pyrethroids [pesticides] results in similar effects.” Typical.

Also not surprisingly, Quackenboss points out that a Zika virus vaccine is in the pipeline and being pushed out as fast as possible. That’s understandable, of course. Before, there was little incentive because the disease was thought to be a disease that made few people more ill than a self-limited viral illness. Add the potential for birth defects if pregnant women are infected, and the urgency of a vaccine increases by at least an order of magnitude. Predictably, though, to Quackenboss insinuates that the Zika scare is all about pushing this vaccine through the pipeline faster, the better to enrich our pharma overlords.

However, to an antivaccine loon, it’s always first and foremost about the vaccines. (Always and forever, amen.) So the conclusion Quackenboss comes to is about as unsurprising as can be:

Lastly, it was just at the end of 2014– 14 months before Zika hysteria– that the Tdap vaccine was mandated for pregnant women in Brazil. The order came down in October, and 10 months later the first cases of microcephaly were seen by local doctors. So these poor women who are eating pesticide-soaked food, breathing pesticide-filled air, and probably drinking pesticide-poisoned water (except that the municipalities don’t even bother to participate in testing) are now vaccinated against their will with a Class C drug with no adequate studies in humans while pregnant.

This is a particularly dumb conspiracy theory, but, then, Quackenboss is an antivaccinationist. If Tdap is causing microcephaly, one wonders why, then, there haven’t been outbreaks of microcephaly in the US, where the CDC has recommended the Tdap vaccine for pregnant women since 2011. Also, the Tdap is recommended in the third trimester, between weeks 27 and 36. That’s long after microcephaly develops, as the standard recommendation to detect microcephaly is to do an ultrasound late in the second trimester or early in the third. In other words, there’s no biological plausibility in blaming microcephaly on the Tdap vaccine because by the time the vaccine is routinely administered, microcephaly has already developed. Not that that stops Quackenboss from characterizing the association of microcephaly with Zika virus infection as “a misdiagnosed non-epidemic of probable pesticide poisoning and vaccine injury fueled by an American media bored with talking about Hillary Clinton’s email server.” As I pointed out last time, Tdap is safe for pregnant women.

Truly, the stupid, it burns.

Of course, I expect this sort of pseudoscientific nonsense from a twit like Quackenboss. I do not expect it from a physician. Unfortunately, all too frequently I do get this sort of stuff from a physician, which is why I’ve never completely retired my schtick about putting a paper bag over my head when physicians say stupid things. In this case, the physician is Dr. Jane Orient, executive director of Association of American Physicians and Surgeons (AAPS). We’ve met Dr. Orient the AAPS before, of course, dating back a long time. It is an organization of physician-cranks (or, if you prefer, crank physicians) that is known for being against vaccine mandates, Medicare (calling it “unconstitutional”), and any form of regulation of health care by government. To top it off, the AAPS has characterized public health programs as “tyranny.” It has also published brain-meltingly bad papers claiming to find that abortion causes breast cancer, has promoted the vile idea that shaken baby syndrome is a misdiagnosis for “vaccine injury,” supported HIV/AIDS denialism, and—of course!—done what all crank medical organizations like to do, attack evidence- and science-based medicine as placing unacceptable limits on physician autonomy. Worse, the AAPS doesn’t even limit itself to medicine in that it’s also published papers attacking anthropogenic global climate change, as though physicians have the necessary expertise to assess climate science. Truly, the crank magnetism and arrogance of the AAPS know no bounds.

Dr. Orient wastes no time demonstrating these traits in her article published—where else?—on WorldNetDaily entitled Zika Virus: What Should We Do About It? I sought it out because, being on the AAPS mailing list, I received a notification of Dr. Orient’s article. Not surprisingly, in it Dr. Orient cites what she calls some “interesting facts”:

  • Brazil had seen an increase in pertussis in fully vaccinated children, so early in 2015 officials mandated immunizing all pregnant women with DTaP (diphtheria/tetanus/acellular pertussis) vaccine, without awaiting proof of efficacy or safety in the developing baby. Only 32 pregnant women were enrolled in a trial of this vaccine, and no results are posted yet.
  • A variable number of months after the vaccinations, the number of microcephaly cases increased from essentially zero in October 2015 to 1,200 in November, and continued to climb.
  • Because of a measles outbreak, there was a major vaccination campaign with MMR (measles/mumps/rubella) in Pernambuco, Brazil, in late 2014. This is a live virus vaccine, and many women likely received it in early pregnancy or shortly before becoming pregnant. Congenital rubella syndrome can cause microcephaly among many other problems, but this was not found in surveillance of American women who inadvertently received MMR around the time of conception.

I can’t help but note here that Dr. Orient actually one-ups the pseudonymous antivaccine loon Quackenboss by coming up with two—two!—different antivaccine conspiracies to blame the increase in cases of microcephaly on instead of Zika virus. That’s hard to do. Instead of just blaming Tdap, she blames the MMR vaccine as well through a tenuous link with congenital rubella syndrome. Of course, many many millions of doses of MMR have been given with no observed association with an increase in birth defects consistent with congenital rubella syndrome. (One notes that congenital rubella syndrome is also associated with autism.) Quite the opposite, in fact. In the US, congenital rubella syndrome has been virtually eliminated, thanks to widespread vaccination with MMR. Seriously, you’d think that Dr. Orient could come up with a more plausible way to link the MMR to microcephaly. That she couldn’t should tell you a lot about the science supporting her other claims about vaccines; i.e., there isn’t any.

Worse, Dr. Orient can’t even get her facts right. DTaP is the vaccine given to children. Tdap is the vaccine given to adults. Tdap is what Brazil started recommending for pregnant women beginning in 2014, because it’s the adult version of the vaccine. She’s also incorrect that there are no studies documetning the safety of the Tdap vaccine in pregnant women. Then, again, there is the aforementioned basic biological implausibility of the hypothesis that Tdap causes microcephaly based on simple embryology and the timing of the vaccination in the third trimester. None of this stops Dr. Orient from plumbing the depths of medical ignorance, though:

The damaged babies are a terrible tragedy. How can we prevent more? Instead of waiting for some future vaccine against a virus that may prove innocent, we could stop transmission now with effective mosquito control in affected areas. We could also immediately stop deliberately exposing women who might be pregnant to medicines or vaccines without thorough safety testing.

In fact, in this conclusion, consistent with her role in the AAPS she can’t resist engaging in a bit of politics, including a little Rachel Carson revisionism. What do I mean by that? Simple. The above paragraph is the final paragraph in her piece; reading it doesn’t tell you what she means by “effective mosquito control.” However, earlier Dr. Orient spelled out what she meant:

The unfortunate babies are being used to promote political causes: legalization of abortion in Latin America, or the fight against “climate change.”

With warmer temperatures, mosquitoes might be able to move further north, it is claimed. But Aedes aegypti arrived in North America around 1980 in a shipment of used tires, not waiting for a temperature increase. And mosquito-transmitted malaria was prevalent in Minnesota during the Little Ice Age. Climate change or not, mosquitoes will not be inconvenienced if we bankrupt our coal industry or ban SUVs.

Travel restrictions would greatly harm the economy of Latin American countries, especially as Brazil is preparing to host the Olympics. Of course, there is no screening at all of illegal entrants to the U.S. The key public health measure is mosquito control. Mosquito-borne diseases, after a time when it was thought that even malaria might be wiped out, began increasing worldwide when the U.S. banned the most effective public health weapon of all time: DDT. If Zika causes rethinking of this disastrous decision, even though other deadly threats like malaria have not, it will save millions of lives – and even help us win the war on bed bugs.

Wow. Anthropogenic climate change denial, demonization of immigrants, and Rachel Carson revisionism, all in one scientifically ignorant package!

If you’ve read Merchants of Doubt by Naomi Oreskes and Erik Conway, you’d be aware that there has been a renewed concerted effort to discredit Rachel Carson, which is what I mean when I refer to “Carson revisionism.” The original effort, of course, occurred immediately after the publication of her highly popular and influential anti-pesticide book Silent Spring and involved the pesticide and chemical industries. However, over the last decade or so, the story of Rachel Carson has been subjected to historical revisionism by the very same people who tried to deny the science demonstrating the harmful health effects of tobacco and who more recently have spearheaded anthropogenic climate change denialism.

It’s beyond the scope of this post to go into detail about the new Rachel Carson revisionism (although I have touched on it before and might do so again in more detail some day), but suffice to say that it involves a narrative in which, because of the anti-pesticide and anti-DDT fervor ignited by her book that led to the banning of DDT in the US, and, if you believe the narrative, in the rest of the world, millions died of malaria that DDT could have saved. Indeed, in a speech railing against climate science, dismissing secondhand tobacco smoke as harmless, and characterizing environmentalism as a “religion,” the arch crank himself, Michael Crichton, characterized the DDT ban as having “caused the deaths of tens of millions of poor people, mostly children, whose deaths are directly attributable to a callous, technologically advanced western society that promoted the new cause of environmentalism by pushing a fantasy about a pesticide, and thus irrevocably harmed the third world.” In his novel State of Fear, Crichton even had one of his characters say, ““Banning DDT killed more people than Hitler.” He even put the death toll at 50 million. Tellingly, the plot of State of Fear involved eco-terrorists plotting mass murder to publicize the dangers of global warming. No wonder Chris Mooney described the novel as “pure porn for global warming deniers.”

There’s only one problem with the revisionist narrative pushed by Crichton before his death and still being promoted by conservative free market-friendly think tanks like the Heartland Institute and the Competitive Enterprise Institute. Although Rachel Carson was certainly not correct about everything (for instance, the evidence linking DDT and cancer turned out to be fairly weak, even over 50 years later), nonetheless this revisionist narrative is demonstrably a load of fetid dingos’ kidneys promoted by the likes of not just Crichton but Steve Milloy, who never met an anti-environmentalism myth he didn’t like, DDT included. The “Rachel Carson killed more people than Hitler” myth is basically a zombie myth that won’t die. In reality, DDT use peaked before Silent Spring and DDT use was decreasing because mosquitos were developing resistance. Sadly, it’s a myth that skeptics who should know better not infrequently fall for, sometimes people I never would have guessed as being susceptible to such messages.

So, if you believe antivaccinationists, it’s not Zika virus that’s causing a surge in cases of microcephaly in Brazil, but—surprise! surprise!—vaccines. And if you believe Dr. Orient and her “brave maverick doctor” pals at the AAPS, the cure is to stop vaccinating reproductive age women, fire up the DDT plants again, and start spraying. Both of them, of course, agree that it’s all the fault of big pharma, which eager to sell a new vaccine against Zika virus, also pushes ever more and more vaccines in order to maximize profits. It’s all logical…if you’re a an antivaccine warrior. Otherwise, not so much.

Where is that paper bag again?

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

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